This research aims to identify the changes in the genetic material itself or its regulation which must occur for mammalian cells to undergo neoplastic progression in response to tumor promoters. Our results suggest that promotability behaves as a dominant trait. Complementation analysis is being carried out to estimate the number of different genes (and gene products) involved in promotability. We found that transfection of whole cell DNA from promotion-sensitive (P+) cells into promotion-resistant (P-) cells results in transfer of promotion sensitivity. Transfection of DNA from nonpromotable cells yield a response to TPA that is no higher than the untransfected background. In addition to P+, DNA retroviral long terminal repeat (LTR) sequences also appear to confer promotion sensitivity on transfection. Whether the P+ sequences specify controlling elements or gene products that are missing from the P- cells is an important question under investigation.